Our overall objective is to further our understanding of the comparative biology of the antitumor action of various human interferons. Our approach at the molecular level will be to use two-dimensional gel electrophoresis and quantitative densitometry to examine the protein profile, i.e., the proteins produced or altered in synthetic rates in interferon-treated clones of established human tumor cell lines and in ascitic fluid and solid tumor samples from patients with ovarian carcinoma. At the cellular level we plan to examine the nature of tumor-lymphocyte-macrophage interactions in primary ovarian carcinoma treated in vitro with interferon in semisolid agar cultures to determine whether, for a given patient, interferon expresses itself via effects on cells of the immune response as well as directly on the tumor. The interferons to be studied include natural interferon-alpha (IFN-alpha), recombinant DNA-produced interferons A and D (IFLrA and IFLrD, respectively), natural interferon-beta (IFN-beta) and natural interferon-gamma (IFN-gamma). The established human tumor lines to be examined include K562 (erythroleukemia), A549 (carcinoma of the lung), 8226 (multiple myeloma) and an ovarian carcinoma line, each chosen because they represent our laboratory-established model for either growth suppression, growth enhancement or no effect in the presence of a given interferon. As the amino acid sequences of most of the interferons to be employed are now known, these studies should provide considerable information on the relationship of the structure of a given interferon to its functions and biological profile. Knowledge of such structure-function relationships will aid in the understanding of the natural role of the interferons, and should be of considerable benefit to those clinicians who design and perform interferon clinical trials, with regard to defining the maximum therapeutic potential and strategy of administration of each interferon.